Accumulation of Dynamic Catch Bonds Between TCR and Agonist Peptide-MHC Triggers T Cell Signaling

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2014 Apr 15

PMID 24725404

Citations 330

Authors

Baoyu Liu

Wei Chen

Brian D Evavold

Cheng Zhu

Affiliations

Soon will be listed here.

Abstract

TCR-pMHC interactions initiate adaptive immune responses, but the mechanism of how such interactions under force induce T cell signaling is unclear. We show that force prolongs lifetimes of single TCR-pMHC bonds for agonists (catch bonds) but shortens those for antagonists (slip bonds). Both magnitude and duration of force are important, as the highest Ca(2+) responses were induced by 10 pN via both pMHC catch bonds whose lifetime peaks at this force and anti-TCR slip bonds whose maximum lifetime occurs at 0 pN. High Ca(2+) levels require early and rapid accumulation of bond lifetimes, whereas short-lived bonds that slow early accumulation of lifetimes correspond to low Ca(2+) responses. Our data support a model in which force on the TCR induces signaling events depending on its magnitude, duration, frequency, and timing, such that agonists form catch bonds that trigger the T cell digitally, whereas antagonists form slip bonds that fail to activate.

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